Method of reducing or treating fibrosis by administering an interleukin-2/TGF-beta receptor fusion polypeptide
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Publication Number
US-12329803-B2
Publication Date
2025-06-17
Expiration Date
Abstract
Provided are multi-functional and multi-valent fusion polypeptides comprising an interleukin polypeptide and two or more TGFβ ligand-binding polypeptides. The compositions and methods provided herein are useful in the application of treating and/or preventing pathogenic infections.
Core Innovation
The patent describes fusion polypeptides for reducing or treating fibrosis in a subject. The fusion polypeptides include an interleukin-2 (IL-2) polypeptide, or a fragment comprising an IL-2 receptor binding domain, linked to two soluble TGFβ receptor II (sTβRII) polypeptides, or fragments comprising ligand binding domains.
The interleukin component comprises an IL-2 receptor binding domain, and the fusion additionally includes ligand binding domains from soluble TGFβ receptor II. The soluble TGFβ receptor II polypeptides are configured as a first and a second sTβRII ligand binding domain within the same fusion polypeptide, and the resulting multi-functional, multi-valent fusion polypeptide is described as sequestering or blocking TGFβ immunosuppression and thereby reducing fibrosis.
The patent further provides extensive embodiment coverage of sequence identity requirements and specified sTβRII components. The IL-2 polypeptide embodiments are defined by amino acid sequence identity requirements, including identity to IL-2 sequence references, and the sTβRII ligand binding embodiments are defined by sequence identity requirements, including identities to sTβRII sequence references and truncation options. The fusion polypeptide is also described as binding or blocking TGFβ isoforms, including TGFβ1, TGFβ2, and TGFβ3.
Claims Coverage
The document contains two independent claims, each directed to a fibrosis-reduction or fibrosis-treatment method using a therapeutically effective amount of a specified fusion polypeptide. The inventive features focus on IL-2 linked to two sTβRII components and an intravenous method using a fusion polypeptide defined by sequence identity to specified SEQ ID NOs.
IL-2 fused to two soluble TGFβ receptor II components for fibrosis reduction
A method of reducing or treating fibrosis in a subject by administering a therapeutically effective amount of a fusion polypeptide comprising an IL-2 polypeptide, or fragment comprising an IL-2 receptor binding domain, and a first soluble TGFβ receptor II polypeptide, or fragment comprising a ligand binding domain, together with a second soluble TGFβ receptor II polypeptide, or fragment comprising a ligand binding domain, thereby reducing or treating fibrosis.
Intravenous treatment with a sequence-identity-defined fusion polypeptide to treat fibrosis
A method of treating fibrosis in a subject by administering intravenously a therapeutically effective amount of a fusion polypeptide comprising an amino acid sequence having at least about 90% sequence identity to any one of SEQ ID NOs: 10-22, wherein the method reduces fibrosis in the subject.
Across the independent claims, fibrosis treatment is achieved by administering a therapeutically effective amount of a fusion polypeptide built around IL-2 receptor binding and soluble TGFβ receptor II ligand binding, with the second independent claim additionally requiring intravenous administration and sequence identity to SEQ ID NOs 10-22.
Stated Advantages
Reduces or treats fibrosis in a subject.
Reduces fibrosis in a subject when administered intravenously.
Documented Applications
Treating fibrosis in a subject in need thereof.
Reducing or treating fibrosis in a subject in need thereof.
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